Association of Toll-like Receptor 3 Polymorphisms with Chronic Hepatitis B and Hepatitis B-Related Acute-on-Chronic Live
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Association of Toll-like Receptor 3 Polymorphisms with Chronic Hepatitis B and Hepatitis B-Related Acute-on-Chronic Liver Failure Yihui Rong,1,2 Haihan Song,3 Shaoli You,2 Bing Zhu,2 Hong Zang,2 Yi Zhao,4 Yongli Li,5 Zhihong Wan,2 Hongling Liu,2 Aimin Zhang,2 Long Xiao,2 and Shaojie Xin2,6
Abstract—Hepatitis B virus (HBV) infection is one of the major causes of chronic liver inflammation. Toll-like receptor 3 (TLR3) plays a key role in innate immunity and is responsible for recognizing viral pathogens. It has been reported that the TLR3 C1234T polymorphism is associated with various diseases. The aim of this study was to investigate whether TLR3 polymorphisms were correlated with susceptibility to chronic HBV infection. Two polymorphisms in the TLR3 gene, A952T and C1234T, were tested by direct sequencing in 452 chronic hepatitis B (CHB) patients and 462 healthy controls. Data showed that subjects carrying 1234CT genotype and TT genotype had 1.42-fold and 2.31-fold increased risk of chronic HBV infection compared to those with CC genotype (95 % confidence interval [CI]01.08–1.86, p00.012; 95 % CI01.34–3.96, p00.002, respectively). Further analysis revealed that the prevalence of 1234CT genotype and T allele was significantly increased in CHB patients with acute-on-chronic liver failure (ACLF) than those without ACLF (odds ratio [OR]01.55, p00.030; OR01.43, p00.040, respectively). These results indicate that TLR3 C1234T polymorphism could be a risk factor for the development of chronic HBV infection, especially the CHB-related ACLF. KEY WORDS: toll-like receptor 3; polymorphism; chronic hepatitis B; acute-on-chronic liver failure.
infection leads to a wide spectrum of outcomes [1]. Although most of the infected individuals can successfully clarify this virus, there are still about 10 % of patients who would develop chronic hepatitis B (CHB) [2]. Among those CHB individuals, some may progress rapidly towards liver failure, a condition referred to as acute-on-chronic liver failure (ACLF) [3]. The outcome of patients with chronic HBV infection is closely related to their immune responses [2]. Toll-like receptors (TLRs) are evolutionary conserved receptors that recognize pathogen-associated molecular patterns and mediate the innate immune responses against invading pathogens [4]. TLRs expressed on immune cells are involved in the uptake and processing of various exogenous and endogenous antigens, such as lipopolysaccharide, viral doublestranded RNA, and unmethylated CpG islands [5]. Upon binding to specific ligands, TLRs promote the maturation of dendritic cells (DCs) and induce production of inflammatory cytokines and activation of adaptive
INTRODUCTION Hepatitis B virus (HBV) infection is one of the major causes of chronic liver inflammation [1]. It is estimated that more than two billion people have been chronically infected by HBV worldwide, and nearly 350 million have become victims of this disease. HBV
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Medical School of Chinese PLA, 28 Fuxing Road, Beijing, 100853, China 2 Liver Failure Treatment and Research Cente
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